A new model for the domain structure of heparan sulfate based on the novel specificity of K5 lyase.
Authors
Murphy, Kevin JMerry, Catherine L R
Lyon, Malcolm
Thompson, James E
Roberts, Ian S
Gallagher, John T
Affiliation
Cancer Research UK and University of Manchester, Department of Medical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.Issue Date
2004-06-25
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Elucidation of the molecular structure of heparan sulfate (HS) is the key to understanding its functional versatility as a co-receptor for growth factors and morphogens. We have identified and exploited the novel substrate specificity of the coliphage K5 lyase in studies of the domain organization of HS. We show that K5 lyase cleaves HS principally within non-sulfated sequences of four or more N-acetylated disaccharides. Uniquely, sections comprising alternating N-acetylated and N-sulfated units are resistant to the enzyme, as are the highly sulfated S domains. Spacing of the K5 lyase cleavage sites ( approximately 7-8 kDa) is similar to that of the S domains. On the basis of these findings, we propose a refined model of the structure of HS in which N-acetylated sequences of four to five disaccharide units (GlcNAc-GlcUA)(4-5) are positioned centrally between the S domains. The latter are embedded within N-acetylated and N-sulfated sequences, forming extended regions of hypervariable sulfation distributed at regular intervals along the polymer chain. K5 lyase provides a means of excision of these composite sulfated regions for structural and functional analyses.Citation
A new model for the domain structure of heparan sulfate based on the novel specificity of K5 lyase. 2004, 279 (26):27239-45 J. Biol. Chem.Journal
The Journal of Biological ChemistryDOI
10.1074/jbc.M401774200PubMed ID
15047699Type
ArticleLanguage
enISSN
0021-9258ae974a485f413a2113503eed53cd6c53
10.1074/jbc.M401774200
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